Redox-responsive Stearic Acid-g-chitosan Oligosaccharide-SS-doxorubicin Conjugates Micelles For Cancer Therapy

In this study, at first, mediated by1-ethyl-3-(3-dimethylami-nopropyl) carbodiimide (EDC), we synthesized stearic acid grafted chitosan oligosaccharide (CSO-SA), which could. Then Redox-responsive stearic acid-g-chitosan oligosaccharide-SS-doxorubicin conjugates (DOX-SS-CSO-SA) was synthesized via disulfide bond between the anticancer drug doxorubicin (DOX) and CSO-SA, using3,3’-dithiobis (succinimidyl propionate)(DSP) as cross linking agent. The DOX-SS-CSO-SA could self-aggregate into micelles in an aqueous medium, and the critical micelle concentration (CMC) was about49.1μg/mL. The micelles had62.8nm number average diameters with a narrow size distribution. The DOX-SS-CSO-SA micelles were relatively stable in moderate physical medium. On the contrary in reductive environment the disulfide linkers in DOX-SS-CSO-SA micelles were cleaved rapidly and the DOX was released. Analyzed with confocal laser scanning microscopy (CLSM), The DOX-SS-CSO-SA micelles presented high efficiency of cellular uptake and rapid intracellular release of the DOX. In vitro antitumor activity tests of DOX-SS-CSO-SA micelles against human liver carcinoma (BEL-7402) cells, human breast carcinoma (MCF-7) cells and the multi-drug resistant (MCF-7/Adr) cells indicated significantly higher cell-killing efficiency than DOX and the reversal activity against DOX resistance MCF-7cells (MCF-7/Adr). And the reversal power was about34.8. In vivo biodistribution studies showed that the DOX-SS-CSO-SA micelles could be enriched into the tumors and had no distribution in hearts. The in vivo antitumor activity results showed that DOX-SS-CSO-SA micelles treatments effectively suppressed the tumor growth and reduced cardiac toxicity caused than commercial doxorubicin hydrochloride injection.